“Our paper is a major advance because we identify a protein that binds to the mutated protein and promotes its breakdown,” he said.
The particular mutation that they studied affects a protein whose function is not well understood. In its normal form, it appears to have multiple sites where other molecules can attach themselves, like a space station with many docking areas.
Several mutations can affect the protein, which is named LRRK2. Some of the mutations cause Parkinson’s disease.
The current theory is that the mutation leads to increased function of LRRK2 and to the formation of abnormal clumps of proteins inside brain nerve cells. The cells eventually die from these effects.
In the current study, the researchers used cultured human kidney cells and found that LRRK2 and a protein called CHIP “robustly” associated with each other.
Further testing showed that CHIP and LRRK2 could bind to each other in two different ways, either directly or indirectly by a third molecule that acted as a bridge.
When CHIP bound to either the normal or mutant form of LRRK2, levels of LRRK2 in the cell decreased, the researchers found. This occurred because the cells increased the rate at which they destroyed LRRK2.
“CHIP may be a useful therapeutic target for treatments to break down LRRK2 in people with Parkinson’s,” Dr. Goldberg said.
“Our next step is to identify cellular mechanisms that signal LRRK2 to be degraded by CHIP or by other mechanisms,” he said. “Because LRRK2 mutations are believed to cause Parkinsonism by increasing the activity of LRRK2, enhancing the normal mechanisms that target LRRK2 for degradation by CHIP may be therapeutically beneficial.”
Lead author Xiaodong Ding, senior research associate in neurology at UT Southwestern, also contributed to the study.
The study was funded in part by the David M. Crowley Foundation.
Visit www.utsouthwestern.org/neurosciences to learn more about UT Southwestern’s clinical services in the neurosciences.
Aline McKenzie | EurekAlert!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy